Comparison of Myelin-Associated Glycoprotein With Vincristine for Facial Nerve Inhibition After Bilateral Axotomy in a TransgenicThy1-GfpRat Model

Abstract

IMPORTANCE Aberrant synkinetic movement after facial nerve injury can lead to prominent facial asymmetry and resultant psychological distress. The current practices of neuroinhibition to promote greater facial symmetry are often temporary in nature and require repeated procedures.OBJECTIVE To determine whether myelin-associated glycoprotein (MAG), a specific neuroinhibitor, can prevent neuroregeneration with efficacy comparable with that of vincristine, a well-established neurotoxin.DESIGN, SETTING, AND PARTICIPANTS Rats transgenic for Thy-1 cell surface antigen-green fluorescent protein (Thy1-Gfp) were randomized into 3 groups. Each rat received bilateral crush axotomy injuries to the buccal and marginal mandibular branches of the facial nerves. The animals received intraneural injection of saline, MAG, or vincristine. MAIN OUTCOMES AND MEASURESThe animals were imaged via fluorescent microscopy at weeks 1, 3, 4, and 5 after surgery. Quantitative fluorescent data were generated as mean intensities of nerve segments proximal and distal to the axotomy site. Electrophysiological analysis, via measurement of compound muscle action potentials, was performed at weeks 0, 3, 4, and 5 after surgery.RESULTS A total of 12 rats were included in the study. Administration of MAG significantly reduced fluorescent intensity of the distal nerve in comparison with the control group at week 3 (mean [SD], MAG group: 94 [11] intensity units vs control group: 130 [11] intensity units; P < .001), week 4 (MAG group: 81 [19] intensity units vs control group: 103 [9] intensity units; P = .004), and week 5 (MAG group: 76 [10] intensity units vs control group: 94 [10] intensity units; P < .001). In addition, rats treated with MAG had greater fluorescent intensity than those treated with vincristine at week 3 (mean [SD], MAG group: 94 [11] intensity units vs vincristine group: 76 [6] intensity units; P = .03), although there was no significant difference for weeks 4 and 5. At week 5, both MAG and vincristine demonstrated lower distal nerve to proximal nerve intensity ratios than the control group (control group, 0.94; vs MAG group, 0.82; P = .01; vs vincristine group; 0.77; P < .001). There was no significant difference in amplitude between the experimental groups at week 5 of electrophysiological testing.CONCLUSIONS AND RELEVANCE Lower facial asymmetry and synkinesis are common persistent concerns to patients after facial nerve injury. Using the Thy1-Gfp rat, this study demonstrates effective inhibition of neuroregeneration via intraneural application of MAG in a crush axotomy model, comparable with results with vincristine. By potentially avoiding systemic toxic effects of vincristine, MAG demonstrates potential as an inhibitor of neural regeneration for patients with synkinesis.LEVEL OF EVIDENCE NA.

Delayed repair of the facial nerve and its negative impacts on nerve and muscle regeneration

“…Furthermore, this experimental model using damage to the buccal branch of the bilateral facial nerve is well tolerated by the animal, as it does not completely deteriorate the animal's motor functions, for the reasons previously mentioned. Other similar studies using this methodology have already been published, demonstrating safe driving for animals and reporting no discomfort to animals [30,31,50,[73][74][75]. However, caution must be taken if the study is conducted with damage to the facial nerve trunk, as it will result in total paralysis of the animal's face.…”

Delivery of Interleukin‐4–Encoding Lentivirus Using Multiple‐Channel Bridges Enhances Nerve Regeneration

“…They were then mounted with ProLong Gold antifade reagent and imaged at 60× magnification via Nikon A1 Confocal Microscope (Nikon). Quantitative data on signal fluorescent intensity were then derived from random sampling of all specimens and controls (Table 2) using MetaMorph Microscopy Automation and Image Analysis Software (Molecular Devices LLC, San Jose, CA) per a previously published protocol 15 …”